Molecular Mechanisms of Neuronal Diversification and Cortical Circuit Assembly

The neocortex consists of two major classes of neurons - excitatory and inhibitory - that are further divided into multiple subtypes based on morphology, electrophysiological properties and gene expression. How these different cell types are generated and how they assemble into diverse circuits remain largely unknown. Recent studies, using single-cell transcriptomics, reveal an unprecedented diversity in neuronal progenitors, and identify putative cell fates in newly-born neurons, before the appearance of clear morphological and physiological features. Surprisingly, we found that metabolic genes are among the most differentially expressed transcripts in distinct classes of interneuron progenitors, suggesting that changes in metabolic states may contribute to cell diversity. Additionally, we identified a group of genes that mark subtypes of inhibitory interneurons before these cells acquire their mature characteristics. Building on these findings, my future research programme aims to understand how specific metabolic states in individual progenitors shape cellular diversity in the neocortex. The second goal of my laboratory is define the gene network and biological pathways that orchestrate the maturation of interneurons and their integration into functional cortical circuits. This work will shed new light on the rules that govern cortical circuit assembly with immediate relevance to cell replacement therapies for brain disorders.